Academic and commercial instrument designers alike have come to over rely on strictly electrostatically- and RF-driven devices for dissociating ions in tandem mass spectrometers, roughly half of which are analyzer-dependent. From a manufacturing point of view, this situation stifles development of new instrumentation, software, and methodology; from a research point of view, it shackles the design and execution of experiments or limits their informational output.
By way of review, there is a family of processes whereby ions can be induced to dissociate (fragment) by interacting with free electrons. These processes, which by various mechanisms force transitions in the precursor ions from bonding energy states to antibonding energy states, are loosely defined by the energy regimes from which the reactant electrons are drawn. In electron-capture dissociation (ECD), free electrons having energies on the order of 1 eV are used to break N—Cα backbone-bonds in multiply protonated (cationic) peptides. [Zubarev R.A. (2003). Reactions of polypeptide ions with electrons in the gas phase. Mass Spectrometry Reviews 22, 57-77.] The term hot ECD is used when ECD experiments are conducted with electrons ranging in energy from 3 to 13 eV. [Kjeldsen F., Haselmann K.F., Budnik B.A., Jensen F., and Zubarev R.A. (2002). Dissociative capture of hot (3-13 eV) electrons by polypeptide polycations: an efficient process accompanied by secondary fragmentation. Chemical Physics Letters 356, 201-206.; Zubarev, 2003]. Electron impact excitation of ions from organics (EIEIO) results from inelastic collisions with electrons ranging in energy from 10 to 20 eV. [Cody R.B. and Freiser B.S. (1979). Electron impact excitation of ions from organics: an alternative to collision induced dissociation. Analytical Chemistry 51, 547-551.] In electron ionization dissociation (EID), cations interact with fast electrons having energies at least 10 eV higher than the ionization threshold of the cations. [Fung, Y.M., Adams, C.M., and Zubarev, R.A. (2009). Electron ionization dissociation of singly and multiply charged peptides. Journal of the American Chemical Society 131, 9977-9985.] In electron-detachment dissociation (EDD, which is the negative-ion counterpart to ECD) [Zubarev, 2003], electrons having energies on the order of 20 eV create positive-radicals or holes in peptidic anions that induce inter-residue bonds in the latter to break. All of these electron-induced dissociation processes, by whatever name has been given them, require that the precursor ions be forced to mingle with a dense population of electrons.
Under current practice with FT ICR (Fourier transform ion cyclotron resonance) mass spectrometers and other radio frequency (RF) devices [e.g., Satake H, Hasegawa H, Hirabayashi A, Hashimoto Y, Baba T. (2007). Fast multiple electron capture dissociation in a linear radio frequency quadrupole ion trap. Analytical Chemistry 79, 8755-8761.], the efficiencies of electron-induced fragmentation processes are fundamentally limited; electrons cannot be trapped at all in linear RF-based devices and only in small numbers in three-dimensional RF-traps (e.g., FT ICR cells). Consequently, there is no practicable way for increasing the density of electrons in reaction cells of these types. This is a major disadvantage for two practical reasons. First the charged-particle capacity of an RF-based device is relatively small; consequently, it is difficult to achieve high yields of product-ions from electron-induced dissociation reactions, which require that a reactant's density (i.e., the number of particles per unit volume) be as high as possible. Second, in terms of detection limit, resolution, and mass accuracy in analyses of organic compounds, FT ICR mass spectrometers are arguably the most powerful in existence; unfortunately, they are also the most expensive to purchase, difficult and expensive to operate and maintain, and ill-suited to the high throughput analyses frequently encountered in proteomics. Although electron-induced dissociation of peptides and proteins was discovered on an FT ICR instrument, the conditions for such reactions are just minimally met in the FT ICR cell. This is because the elementary physics of a collision between an electron and a molecular ion dictates that the energy necessary for any given electron-induced dissociation reaction be supplied almost entirely by the electron. Therefore, the design of any practical electron-induced dissociation cell should include a means for controlling both the average energy of the electrons and the width of the distribution about this average. This, however, is fundamentally impossible to accomplish in an FT ICR cell, and because of fundamental constraints on the latter's geometry and operation, the prospects for improving this circumstance are poor. Moreover, ECD based on FT ICR mass spectrometers became a practicable technique only after hollow dispenser (indirectly heated) cathodes were implemented in the ICR cell. Use of these cathodes solved two problems at once—the bigger emitting area provided better spatial overlapping between electrons and ions, and the higher electron yield increased the number of electron capture events. However, dispenser cathodes cannot tolerate vacuum pressures higher than 10−7 Torr. In an FT ICR mass spectrometer, the dispenser cathode is situated outside of the ICR cell, which is a region of very low pressure.
In principle, a large number of electrons can be trapped in a hybrid electromagnetostatic (EMS) cell. There are, however, technical obstacles that must be overcome in order for these electrons to occupy the same volume as the ions with which the electrons must react. (See Voinov V G, Deinzer M L, Barofsky D F. Rapid Commun. Mass Spectrom. 2008; 22: 3087; Voinov V G, Deinzer M L, Barofsky D F. Anal. Chem. 2009; 81: 1238; Voinov V G, Deinzer M L, Beckman J S, Barofsky D F. J. AM Soc. Mass Spectrom. 2011, 22, 607; and, Voinov V G, Beckman J S, Deinzer M L, Barofsky D F. Rapid Commun. Mass Spectrom. 2009, 23, 3028.) Accordingly, a need remains for devices and methods for dissociating ions in mass spectrometers that are not restricted by such limitations.